A Simple and Efficient Method for Synthesis of sn-Glycero-Phosphoethanolamine

Lipids. 2020 Jul;55(4):395-401. doi: 10.1002/lipd.12243. Epub 2020 May 13.

Abstract

An efficient three-step strategy for the convenient synthesis of Sn-glycero-3-phosphoethanolamine (GroPEtn) from a commercially available 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) is reported. Direct hydrolysis of DPPE produces a complex inseparable mixture, hence a protection and deprotection strategy is employed to prepare GroPEtn. The primary amine of DPPE is protected with a highly stable acid-labile trityl group, followed by strong base hydrolysis of N-trityl-DPPE gives N-trityl-GroPEtn. Further a mild, rapid, and efficient deprotection method is established using trifluoroacetic acid to remove N-trityl moiety, affords GroPEtn as a single product. This is the first semisynthetic approach and efficient method to produce GroPEtn with a total yield of 66% in three steps. GroPEtn did not show any cytotoxicity against human kidney (HK-2) cells and reporter gene assay for activation of Keap1-Nrf2-mediated antioxidant defense mechanism showed no significant effects.

Keywords: Acid hydrolysis; Glycerophospholipids; High-resolution mass spectrometry; Nuclear-magnetic resonance; Trityl deprotection; sn-glycero-phosphoethanolamine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Proliferation
  • Humans
  • Kelch-Like ECH-Associated Protein 1 / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Phosphatidylethanolamines / chemical synthesis*
  • Phosphatidylethanolamines / chemistry*
  • Phosphatidylethanolamines / pharmacology
  • Trifluoroacetic Acid / chemistry

Substances

  • KEAP1 protein, human
  • Kelch-Like ECH-Associated Protein 1
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Phosphatidylethanolamines
  • glycerophosphoethanolamine
  • 1,2-dipalmitoyl-3-phosphatidylethanolamine
  • Trifluoroacetic Acid